| Eligibility |
Inclusion Criteria:
1. Men and women of 18 years of age and older
2. Voluntary agreement to provide written informed consent and the willingness and
ability to comply with all aspects of the protocol.
3. Have histologically confirmed FL, grades 1 to 3a. Subjects may have
relapsed/refractory disease following at least 2 standard prior systemic treatment
regimen where at least 1 anti-CD20-based regimen was used.
4. Eastern Cooperative Oncology Group (ECOG) score of 0 </= 2
5. Treatment recommended in accordance with the GELF criteria due to the presence of at
least one of the following:
- Any nodal or extranodal tumor mass >7 cm diameter
- Involvement of at least 3 nodal sites, each with diameter >3 cm
- Presence of any systemic or B symptoms
- Splenic enlargement with inferior margin below the umbilical line
6. Compression syndrome (ureteral, orbital, gastrointestinal)
7. Pleural or peritoneal serous effusion (irrespective of cell content)
8. Leukemic phase (>5.0 x 109/L circulating malignant cells)
9. Cytopenias (granulocyte count <1.0 x 109/L and/or platelets <100 x 109/L)
10. Meet the following laboratory parameters:
- ANC = 750 cells/µL (0.75 x 109/L), or = 500 cells/µL (0.50 x 109/L) in subjects
with documented bone marrow involvement
- Platelet count = 50,000 cells/µL (50 x 109/L), or = 30,000 cells/µL (30 x 109/L)
in subjects with documented bone marrow involvement, and without transfusion
dependence.
- Serum AST and ALT/SGPT = 3.0 x ULN, unless related to disease involvement
- Total bilirubin = 1.5 x ULN, unless due to disease involvement, Gilbert's, or
hemolytic anemia).
- Estimated creatinine clearance (ie, eGFR using Cockcroft-Gault) = 40 mL/min.
11. No prior therapy with EZH2 inhibitors
12. At least one bi-dimensionally measurable nodal lesion > 1.5 cm in its longest diameter
by CT scan or MRI excluding lesions that meet the following criteria
- Previously irradiated lesions should not be counted as target lesions
- Lesions that are intended to be used to collect tissue samples for biopsy should
not be counted as target lesions
- Bone lesions should not be counted as target lesions
13. All clinically significant treatment-related toxicity from prior therapy, except for
alopecia, resolved to = Grade 1 or to a new stable baseline
14. Female subjects of reproductive potential must have a negative urine/serum\ pregnancy
test upon study entry. Female subjects who are of non-reproductive potential (ie,
post-menopausal by history - no menses for =1 year; OR history of hysterectomy; OR
history of bilateral tubal ligation; OR history of bilateral oophorectomy) are exempt
from pregnancy testing.
15. Male and female subjects of reproductive potential who agree to use both a highly
effective method of birth control (eg, implants, injectables, combined oral
contraceptives, some intrauterine devices [IUDs], complete abstinence1, or sterilized
partner) and a barrier method (eg, condoms, cervical ring, sponge, etc) during the
period of therapy and for 12 months after the last dose of rituximab.
16. Men and women must agree to refrain from sperm or oocyte donation during the study and
for 12 months after the last dose of rituximab.
Exclusion Criteria:
1. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
2. Transformed Follicular lymphoma
3. Any uncontrolled illness including, but not limited to, significant active infections,
hypertension, angina, arrhythmias, pulmonary disease, or autoimmune dysfunction
4. Subjects who have tested positive for hepatitis B surface antigen and/or hepatitis B
core antibody plus have a hepatitis B polymerase chain reaction (PCR) assay (subjects
with a negative PCR assay are permitted with appropriate anti-viral prophylaxis)
5. Positive for hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV)
antibody; subjects with positive hepatitis C antibody are eligible if they are
negative for hepatitis C virus by PCR
6. Other diagnosis of cancer that is likely to require treatment in the next 2 years,
with the exception of the following:
- Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin
- Curatively treated carcinoma in situ of the cervix
- Hormonal therapy for prostate cancer
7. History of clinically significant cardiovascular abnormalities such as congestive
heart failure (New York Heart Association classification = 2), myocardial infarction
within 6 months of study entry
8. History of clinically significant gastrointestinal (GI) conditions, particularly:
- Known GI condition that would interfere with swallowing or the oral absorption or
tolerance of study drug
- Pre-existing malabsorption syndrome or other clinical situation that would affect
oral absorption
9. Females who are currently breastfeeding
10. Received a live virus vaccination within 28 days of first dose of Rituxan
11. Participation in a separate investigational therapeutic study
12. Psychiatric illness/social situations that would interfere with study compliance
|
